The skin redoxome.

Redoxome is the network of redox reactions and redox active species (ReAS) that affect the homeostasis of cells and tissues. Due to the intense and constant interaction with external agents, the human skin has a robust redox signalling framework with specific pathways and magnitudes. The establishment of the skin redoxome concept is key to expanding knowledge of skin disorders and establishing better strategies for their prevention and treatment. This review starts with its definition and progress to propose how the master redox regulators are maintained and activated in the different conditions experienced by the skin and how the lack of redox regulation is involved in the accumulation of several oxidation end products that are correlated with various skin disorders.

Antimicrobial resistance, diarrheagenic and avian pathogenic virulence genes in Escherichia coli from poultry feed and the ingredients / Resistência antimicrobiana, genes de virulência diarreiogênicos e patogênicos para aves em Escherichia coli isoladas de ingredientes e ração de frangos

Diarrheagenic (DEC) and avian pathogenic Escherichia coli (APEC) are associated with intestinal and extra-intestinal infections (ExPEC), respectively. We aimed to analyze the antimicrobial susceptibility, gene encoding virulence factors associated to DEC and APEC, and phylogenetic classification in E. coli isolated from 320 samples of feed and ingredients. Antimicrobial susceptibility was performed using the disk diffusion method and Multiple Antibiotic Resistance (MAR) Index and Multi-Drug Resistance (MDR) were calculated. Phylogenetic classification was performed on samples harboring DEC and/or APEC virulence-associated genes. A total of 110 E. coli strains were isolated in 15% (49/320) of the evaluated inputs (n=13 vegetable meal; n=33 animal meal, n=3 feed). In general, the isolates showed the highest rates of antimicrobial resistance to sulfonamide and cefazolin and 18% (20/110) were multi-drug resistant. MAR index of feed samples was the highest (0.467). Six and five strains had APEC and DEC virulence-associated genes, respectively, and belonging to phylogenetic groups A and B1. These findings point to the need for strict microbiological control during the production process of these foods.(AU)

Escherichia coli diarreiogênicas (DEC) e patogênicas para aves (APEC) são associadas a infecções intestinais e extraintestinais (ExPEC), respectivamente. O objetivo do presente trabalho foi avaliar a sensibilidade antimicrobiana, a presença de genes que codificam os fatores de virulência relacionados à DEC e APEC, e a classificação filogenética em E. coli isoladas de 320 amostras de ração para frangos e ingredientes. A sensibilidade antimicrobiana foi determinada pelo método disco-difusão e calculou-se o índice de resistência múltipla aos antimicrobianos (IRMA) e a resistência a múltiplas drogas (MDR). Nas amostras que possuíam genes de virulência relacionados à DEC e/ou APEC, foi realizada a classificação filogenética. Foram isoladas 110 amostras de E. coli em 15% (49/320) dos insumos avaliados (n=13 farelos vegetais; n=33 farinhas de origem animal; n=3 rações). De forma geral, os isolados apresentaram as maiores frequências de resistência antimicrobiana à sulfonamida e à cefazolina e 18% (20/110) foram resistentes a múltiplas drogas. O IRMA das rações foi o mais alto (0,467). Os genes que codificam fatores de virulência associados à APEC e DEC foram detectados em seis e cinco isolados, respectivamente, pertencentes aos grupos filogenéticos A e B1. Os resultados demonstram a necessidade de rigoroso controle microbiológico durante o processo de produção desses alimentos.(AU)

Brachyury oncogene is a prognostic factor in high-risk testicular germ cell tumors.

The T-box transcription factor Brachyury has been considered a cancer-specific marker and a novel oncotarget in solid tumors. Brachyury overexpression has been described in various cancers, being associated with epithelial-mesenchymal transition, metastasis, and poor prognosis. However, its clinical association with testicular germ cell tumor is unknown. We analyzed the expression of Brachyury by immunohistochemistry in a series of well-characterized testicular germ cell tumor samples and at transcript level by in silico analysis. Additionally, we aimed to investigate the clinical significance of Brachyury in testicular germ cell tumor. Brachyury cytoplasm immunostaining was present in 89.6% (86/96) of cases with nuclear staining observed in 24% (23/96) of testicular germ cell tumor. Bioinformatics microarray expression analysis of two independent cohorts of testicular germ cell tumors showed similar results with increased levels of Brachyury in testicular germ cell tumors and metastasis compared with normal testis. Clinically, Brachyury nuclear staining was statistically associated with lower event-free survival (p = 0.04) and overall survival (p = 0.01) in intermediate/high-risk testicular germ cell tumors. Univariate analysis showed that Brachyury nuclear subcellular localization was a predictor of poor prognosis (p = 0.02), while a tendency was observed by multivariate analysis (HR: 3.56, p = 0.06). In conclusion, these results indicate that Brachyury plays an oncogenic role in testicular germ cell tumors and its subcellular localization in the nucleus may constitute a novel biomarker of poor prognosis and a putative oncotarget for intermediate/high-risk testicular germ cell tumor patients.

Absence of microsatellite instability and BRAF (V600E) mutation in testicular germ cell tumors.

Testicular germ cell tumors (TGCT) are the most common malignant neoplasm in young men. DNA mismatch repair deficiency can lead to microsatellite instability (MSI), an important mechanism of genetic instability. A mutation of the BRAF gene has been implicated in the pathogenesis of several solid tumors and has recently become an important therapeutic target. The role of MSI and BRAF gene mutation in TGCT, particularly in refractory disease, is poorly understood and reported findings are controversial. In this study, we aimed to determine the frequency and clinical impact of MSI status and BRAF mutations in TGCT. DNA was isolated from formalin-fixed paraffin embedded (FFPE) tissue from 150 TGCT cases. The MSI phenotype was evaluated using multiplex PCR for five quasimonomorphic mononucleotide repeat markers. Exon 15 of the BRAF oncogene (V600E) was analyzed by PCR, followed by direct sequencing. Sixteen percent of cases were considered to have refractory disease. In a small subset of cases (17 for MSI and 18 for BRAF), the quantity and quality of DNA recovery were poor and therefore, were unable to be analyzed. The remaining 133 TGCT cases showed a complete absence of MSI. Of the 132 cases successfully evaluated for BRAF mutations, all were V600E wild-type. In conclusion, despite a distinct response of testicular germ cell tumors to therapy, microsatellite instability, and the BRAF V600E mutation were absent in all testicular germ cell tumors tested in this study.

Impact or push-off lameness presentation is not altered by the type of track surface where horses are trotted / Claudicação de impacto ou elevação não é alterada pelo tipo de superfície onde os cavalos são troteados

This study aimed to evaluate the influence of the track surface on which horses are examined, regarding the phase of lameness presentation. Ten horses with lameness in at least one limb were evaluated with wireless inertial sensors on three track surfaces (concrete, loose sand and grass). Six crossover track sequences were established. The variables vector sum, maximum and minimum height of the head and pelvis, variation coefficient of the maximum and minimum height of the head and pelvis were analyzed using ANOVA, followed by Tukey test to compare means between track surface and sequence, at 5% significance level. The lameness phase (impact or pushoff) was analyzed considering the proportion of affected animals. There were no differences on vector sum, maximum and minimum height or variation coefficient of head and pelvis. Difference was observed on the number of strides registered on sand compared to grass and concrete (p <0.0001) for fore and hindlimbs. Impact lameness on forelimbs was presented by a larger number of animals on the concrete surface; pushoff lameness was more evident on the grass surface. In the hindlimbs, impact lameness was more evident on the grass surface, while pushoff lameness was in greater number of animals on concrete surfaces. The track sequence on which horses were trotted during evaluation does not seem to be a factor, but the number of lame horses and the phase of lameness manifestation can vary between track surfaces, as some horses showed impact lameness on soft ground and elevation lameness on hard ground.

Este estudo teve como objetivo avaliar a influência do tipo de superfície em que os cavalos são examinados em relação à fase de apresentação da claudicação. Dez cavalos com claudicação em pelo menos um dos membros foram avaliados com sensores inerciais sem fio em três tipos de superfície (concreto, areia e grama). Seis sequências de cruzamento de tipo de superfície foram estabelecidas. As variáveis soma vetorial, altura máxima e mínima da cabeça e da pélvis, o coeficiente de variação da altura máxima e mínima da cabeça e da pélvis foram analisadas utilizando uma Análise de Variância, seguida do teste de Tukey para comparação das médias entre tipos de superfície e sequências, a um nível de significância de 5%. A fase da claudicação (impacto ou elevação) foi analisada considerando a proporção de animais afetados. Não houve diferença na soma vetorial, altura máxima ou mínima e coeficiente de variação da altura máxima e mínima da cabeça e pélvis. Foi observada diferença no número de passos registrados na areia em comparação com grama e concreto (p <0,0001) para membros torácicos e pélvicos. Claudicação de impacto nos membros torácicos foi apresentada em um número maior de animais na superfície de concreto, já claudicação de elevação foi mais evidente na superfície de grama. Em membros pélvicos, a claudicação de impacto foi mais evidente na superfície de grama, enquanto claudicação de elevação esteve em maior número de animais na superfície de concreto. A sequência de superfícies em que os cavalos foram troteados durante a avaliação não foi um fator importante na manifestação da claudicação, mas o número de cavalos claudicantes e a fase de manifestação da claudicação podem variar entre as superfícies, visto que alguns cavalos mostraram claudicação de impacto em solo macio e claudicação de elevação em solo duro.

Placement of dental implants in the maxillary tuberosity: a systematic review.

The aim of this systematic review was to identify clinical studies on implants placed in the tuberosity region to determine the survival rate of these implants when compared to implants placed in other regions of the maxilla. A search for data published up until March 2014 was undertaken using the PubMed, Cochrane Library, Embase, and ScienceDirect databases. Eligible studies were selected according to inclusion and exclusion criteria. The first database search revealed 310 titles. After inclusion and exclusion criteria were applied, five studies remained for the detailed analysis. A total of 113 patients were followed for a period of 6-144 months; 289 implants were placed in the patients evaluated. There were eight failures/losses of dental implants in the tuberosity region; the overall survival rate was 94.63% for these implants. In controlled studies, the cumulative survival rates for implants placed in the maxillary tuberosity and other maxillary regions were 96.1% and 95%, respectively. In conclusion, implants placed into the maxillary tuberosity are a predictable alternative for the treatment of patients with insufficient bone volume in the maxillary region. However, randomized trials are needed to assess the effectiveness of this treatment.

Cytogenetic studies of Brazilian pediatric myelodysplastic syndrome cases: challenges and difficulties in a large and emerging country.

Myelodysplastic syndromes (MDS) and juvenile myelomonocytic leukemia (JMML) are rare hematopoietic stem cell diseases affecting children. Cytogenetics plays an important role in the diagnosis of these diseases. We report here the experience of the Cytogenetic Subcommittee of the Brazilian Cooperative Group on Pediatric Myelodysplastic Syndromes (BCG-MDS-PED). We analyzed 168 cytogenetic studies performed in 23 different cytogenetic centers; 84 of these studies were performed in patients with confirmed MDS (primary MDS, secondary MDS, JMML, and acute myeloid leukemia/MDS+Down syndrome). Clonal abnormalities were found in 36.9% of the MDS cases and cytogenetic studies were important for the detection of constitutional diseases and for differential diagnosis with other myeloid neoplasms. These data show the importance of the Cooperative Group for continuing education in order to avoid a late or wrong diagnosis.

Cytogenetic studies of Brazilian pediatric myelodysplastic syndrome cases: challenges and difficulties in a large and emerging country

Myelodysplastic syndromes (MDS) and juvenile myelomonocytic leukemia (JMML) are rare hematopoietic stem cell diseases affecting children. Cytogenetics plays an important role in the diagnosis of these diseases. We report here the experience of the Cytogenetic Subcommittee of the Brazilian Cooperative Group on Pediatric Myelodysplastic Syndromes (BCG-MDS-PED). We analyzed 168 cytogenetic studies performed in 23 different cytogenetic centers; 84 of these studies were performed in patients with confirmed MDS (primary MDS, secondary MDS, JMML, and acute myeloid leukemia/MDS+Down syndrome). Clonal abnormalities were found in 36.9% of the MDS cases and cytogenetic studies were important for the detection of constitutional diseases and for differential diagnosis with other myeloid neoplasms. These data show the importance of the Cooperative Group for continuing education in order to avoid a late or wrong diagnosis.

Acute effects of resistance exercise and intermittent intense aerobic exercise on blood cell count and oxidative stress in trained middle-aged women

The aim of this study was to compare the effect of an intermittent intense aerobic exercise session and a resistance exercise session on blood cell counts and oxidative stress parameters in middle-aged women. Thirty-four women were selected and divided into three groups: RE group (performing 60 min of resistance exercises, N = 12), spinning group (performing 60 min of spinning, N = 12), and control group (not exercising regularly, N = 10). In both exercise groups, lymphocytes and monocytes decreased after 1-h recuperation (post-exercise) compared to immediately after exercise (P < 0.05). Immediately after exercise, in both exercised groups, a significant increase in TBARS (from 16.5 ± 2 to 25 ± 2 for the spinning group and from 18.6 ± 1 to 28.2 ± 3 nmol MDA/mL serum for the RE group) and protein carbonyl (from 1.0 ± 0.3 to 1.6 ± 0.2 for the spinning group and from 0.9 ± 0.2 to 1.5 ± 0.2 nmol/mg protein for the RE group) was observed (P < 0.05). A decrease in antioxidant activities (non-protein sulfhydryl, superoxide dismutase, catalase) was also demonstrated with a negative correlation between damage markers and antioxidant body defenses (P < 0.05). These results indicate that an acute bout of intermittent or anaerobic exercise induces immune suppression and increases the production of reactive oxygen species, causing oxidative stress in middle-aged and trained women. Furthermore, we demonstrated that trained women show improved antioxidant capacity and lower oxidative damage than sedentary ones, demonstrating the benefits of chronic regular physical activity.

Molecular genetic analysis of bilateral ovarian germ cell tumors.

BACKGROUND: Ovarian germ cell tumors (oGCTs) are rare and highly heterogeneous with regard to their clinical and histologic appearance. The risk of tumor development is higher in children with aberrant sexual differentiation. Development of gonadoblastomas is seen in young women with 46,XY gonadal dysgenesis. At least 50 % of gonadoblastomas may develop into malignant oGCTs, mostly dysgerminomas. In this study, we evaluated bilateral oGCTs in clinically inapparent patients for sex chromosomal aberrations. PATIENTS AND METHODS: We analyzed tumor samples of 15 patients with synchronous bilateral oGCTs enrolled onto the consecutive MAKEI trials for non-testicular GCTs. Paraffin embedded samples from the Kiel German Childhood Tumor Registry were evaluated for the presence of Y-chromosomal sequences. Molecular genetic techniques included comparative genomic hybridization, polymerase chain reaction, and fluorescence in situ hybridization. RESULTS: Among 15 patients with bilateral oGCTs, Y-chromosomal DNA sequences were detected in 6 tumors. Both mature teratomas were negative for Y-chromosomal DNA. Thus, 5 of 12 malignant oGCTs and 1 immature teratoma (with elevated AFP) showed Y-chromosomal material. A 45(X,0) karyotype could not be demonstrated. CONCLUSIONS: These investigations provide additional insight into the development of oGCTs: mature teratomas, which develop from postmeiotic germ cells, are not associated with gonadal dysgenesis. Bilateral immature teratomas, dysgerminomas and mixed malignant oGCTs may frequently show Y-chromosomal DNA, indicating underlying but clinically inapparent gonadal dysgenesis. Thus, the presence of aberrant Y-chromosomal sequences appears to be involved in tumor development in about half of these patients.